Mutations predictive of hyperactive Ras signaling correlate with inferior survival across high-risk pediatric acute leukemia.
Integrative clinical sequencing (ICS)
Ras
pediatric leukemia
Journal
Translational pediatrics
ISSN: 2224-4344
Titre abrégé: Transl Pediatr
Pays: China
ID NLM: 101649179
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
entrez:
11
3
2020
pubmed:
11
3
2020
medline:
11
3
2020
Statut:
ppublish
Résumé
Cancer remains the number one cause of disease-related mortality in children, and despite advances in the molecular understanding of leukemia and targeted therapies, refractory leukemia remains a leading cause of death. It therefore is essential to further define features, e.g., To gain insights into the genetic drivers predictive of aggressive clinical behavior among pediatric leukemia patients, we performed comprehensive integrative clinical sequencing (ICS), including paired tumor/normal DNA sequencing and RNA-seq, for pediatric patients who presented at our institution over a period of five years with acute lymphoblastic or myelogenous leukemia (ALL and AML; n=43) and high-risk clinical features (high white blood cell count, extramedullary disease, or refractory and/or relapsed disease). We found that We thus propose that hyperactive Ras signaling confers inferior survival in high-risk pediatric acute leukemia and that Ras pathways should be molecularly characterized to inform clinical decision making and to identify patients for experimental clinical trials and RAS-targeted therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer remains the number one cause of disease-related mortality in children, and despite advances in the molecular understanding of leukemia and targeted therapies, refractory leukemia remains a leading cause of death. It therefore is essential to further define features, e.g.,
METHODS
METHODS
To gain insights into the genetic drivers predictive of aggressive clinical behavior among pediatric leukemia patients, we performed comprehensive integrative clinical sequencing (ICS), including paired tumor/normal DNA sequencing and RNA-seq, for pediatric patients who presented at our institution over a period of five years with acute lymphoblastic or myelogenous leukemia (ALL and AML; n=43) and high-risk clinical features (high white blood cell count, extramedullary disease, or refractory and/or relapsed disease).
RESULTS
RESULTS
We found that
CONCLUSIONS
CONCLUSIONS
We thus propose that hyperactive Ras signaling confers inferior survival in high-risk pediatric acute leukemia and that Ras pathways should be molecularly characterized to inform clinical decision making and to identify patients for experimental clinical trials and RAS-targeted therapy.
Identifiants
pubmed: 32154134
doi: 10.21037/tp.2019.12.03
pii: tp-09-01-43
pmc: PMC7036640
doi:
Types de publication
Journal Article
Langues
eng
Pagination
43-50Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL132392
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007622
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006508
Pays : United States
Informations de copyright
2020 Translational Pediatrics. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors have no conflicts of interest to declare.
Références
Blood. 2005 Sep 15;106(6):2113-9
pubmed: 15951308
Blood. 2011 Jul 14;118(2):243-51
pubmed: 21562038
Nat Rev Clin Oncol. 2015 Jun;12(6):344-57
pubmed: 25781572
JAMA. 2015 Sep 1;314(9):913-25
pubmed: 26325560
Cancer Cell. 2013 Dec 9;24(6):710-24
pubmed: 24332040
Leukemia. 2018 Apr;32(4):931-940
pubmed: 28972594
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2548-53
pubmed: 24550281
Nat Genet. 2015 Nov;47(11):1326-1333
pubmed: 26457647
Nat Genet. 2015 Aug;47(8):864-71
pubmed: 26121087
Blood. 2002 Sep 1;100(5):1532-42
pubmed: 12176867
Blood. 2017 Aug 10;130(6):732-741
pubmed: 28588019
Nature. 2013 Dec 5;504(7478):143-147
pubmed: 24284627
Blood. 2014 Nov 27;124(23):3420-30
pubmed: 25253770
Cancer Discov. 2019 Aug;9(8):1050-1063
pubmed: 31088841
Blood. 2011 Nov 17;118(20):5593-603
pubmed: 21881046
N Engl J Med. 2017 Feb 9;376(6):536-547
pubmed: 28177873
Blood. 1999 May 1;93(9):3074-80
pubmed: 10216104
Nat Genet. 2015 Apr;47(4):330-7
pubmed: 25730765
Blood. 2017 Aug 10;130(6):722-731
pubmed: 28588020
Nature. 2018 Mar 15;555(7696):371-376
pubmed: 29489755
Blood. 2016 Aug 4;128(5):686-98
pubmed: 27288520
Nature. 2014 Feb 20;506(7488):328-33
pubmed: 24522528
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Blood. 2003 Aug 15;102(4):1474-9
pubmed: 12702504
Nat Genet. 2016 Dec;48(12):1551-1556
pubmed: 27798625
Nat Genet. 2013 Mar;45(3):242-52
pubmed: 23334668
Blood Cancer J. 2017 Feb 3;7(2):e523
pubmed: 28157215
Nat Med. 2018 Jan;24(1):103-112
pubmed: 29227476
Nature. 2018 Mar 15;555(7696):321-327
pubmed: 29489754
Pediatr Blood Cancer. 2018 Feb;65(2):
pubmed: 28853218
J Clin Oncol. 2017 Mar 20;35(9):975-983
pubmed: 28297628
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11306-11311
pubmed: 27655895
Blood. 2015 Jun 25;125(26):3977-87
pubmed: 25999453
Nature. 2012 Jan 11;481(7380):157-63
pubmed: 22237106